The overall aim of the proposed project is the study of the factors which regulate breathing in the mature fetus, which alter respiratory sensitivity over birth and which determine the stability of respiration in the newborn period. The results are intended to form the basis of a more rational approach to the treatment of infants who develop respiratory difficulties at or after birth. The experiments will extend those being carried out in the present project period. There are five groups. First, we shall try and identify the nature of the inhibitory process in the mature sheep fetus which isolates respiratory and other motor neurones from sensory inputs and we shall look in particular for evidence that opiate-like substances, elaborated by fetus or placenta are involved. Secondly, we shall determine whether and how far a reflex originating in pressure-sensitive receptors in the atria and vessels close to the heart are involved in the increase in drive to ventilation at birth. Thirdly, we shall use a recently developed, rapid-response CO2 electrode to record the true levels of CO2 in arteries and the gradients of CO2 which develop with occlusion of the umbilical cord and the onset of respiration. This should give us the true stimulus to ventilation at this critical period. Fourthly, we shall continue current studies on the mode of activation of the carotid body chemoreceptors at birth. The present evidence suggests strongly that a vascular mechanism is responsible and we shall use recently developed methods which record changes in local blood flow in tissue using hydrogen generation and clearance and methods for recording the distribution of red cells and Hb-O2 saturation in carotid body tissue. Finally, we shall continue present studies which involve the construction of a model of respiratory control in the newborn and from this to determine the factors which make respiration stable or unstable and by comparing the operation of this model with the traces obtained from normal infants, premature infants and infants with known respiratory or vascular lesions, we anticipate finding out whether respiration is stable.